Onset of Reduced Ca2+Sensitivity of Tension During Stunning in Porcine Myocardium

Recent data suggest that reduced Ca2+sensitivity of tension is a mechanism of the post-ischemic myocardial dysfunction, termed stunning. The purpose of the present study was to determine whether the decrease in myofilament Ca2+sensitivity occurs during ischemia or during the subsequent period of reperfusion. Serial biopsies from anin vivoopen-chest porcine model of regional LAD myocardial stunning (n=6) were used to obtainin vitromeasurements of Ca2+sensitivity of tension in myocardium from the LAD bed. Regional ventricular myocardial function was assessed from percentage systolic myocardial wall thickening (%Th) and the load-independent end-systolic pressure wall thickness relation (ESPTR). Stunning was induced by 45 min of low flow LAD ischemia (43±4 ml/min/100 gm) followed by 30 min of reperfusion with control aerobic flow (117±7 ml/min/100 g). Endocardial biopsies were obtained from the LAD bed during pre-ischemia, ischemia (immediately prior to reperfusion), and post-ischemia (after 30 min of reperfusion). Biopsies were mechanically disrupted and single cell-sized preparations of permeabilized myocardium were attached to a force transducer to measure directly steady-state tension-pCa relationships. The %Th decreased to 7±11% of control during ischemia (P<0.001) and returned to 30±11% of control in the post-ischemic stunned state (P<0.001). Stunning resulted in a significant leftward shift of the ESPTR as compared to control, indicating depressed regional myocardial function. The pCa (-log [Ca2+] ) for half maximal activation of tension, i.e. pCa50, was 5.96±0.04 in control myocardium and was unchanged during ischemia (5.95±0.03), but significantly decreased to 5.82±0.04 upon reperfusion (P<0.05). These data show that the decrease in Ca2+sensitivity of tension associated with stunning occurs during reperfusion, and supports the idea that reperfusion injury is a mechanism of myocardial stunning.